{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nExportin‐5 (XPO5) functions as a critical nuclear export receptor that operates in a RanGTP‐dependent manner to recognize and transport double‐stranded RNA substrates—most notably, precursor microRNAs (pre‐miRNAs). XPO5 binds specifically to correctly processed pre‐miRNAs by engaging structural motifs such as the characteristic 2‐nucleotide 3′ overhang and the double‐stranded stem, thereby ensuring efficient and accurate miRNA biogenesis. Structural and biochemical studies further reveal that XPO5, in complex with RanGTP, forms a protective “baseball mitt”–like cage around the pre‐miRNA, coordinating nuclear and cytoplasmic processing steps. In addition, competitive interactions with regulatory RNAs and proteins modulate its affinity for cargo, and aberrancies such as point mutations or saturation by excess RNA regulators can compromise pre‐miRNA export and downstream miRNA maturation processes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role in pre‐miRNA export, XPO5 is also implicated in the nucleocytoplasmic trafficking of several other RNA species and associated protein cofactors. For example, it participates in the export of aminoacylated tRNAs in association with translation elongation factor eEF1A, and contributes to the export of ribosomal subunits, thereby influencing ribosome assembly and overall protein synthesis. These additional functions underscore its broader significance in regulating the cellular distribution of RNA and protein regulators."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAlterations in XPO5—ranging from single‐nucleotide polymorphisms and mutations to post‐translational modifications such as SUMOylation—have been tightly linked to human disease. In various cancers (including thyroid, melanoma, hepatocellular, and prostate carcinomas) and other disorders, differential expression or modification of XPO5 disrupts miRNA homeostasis and is associated with tumor initiation, progression, and altered therapeutic responses. Moreover, studies have revealed that specific genetic variants in the XPO5 gene correlate with disease susceptibility and prognosis across multiple clinical contexts (from colorectal and renal pathologies to cardiovascular conditions and lead poisoning), highlighting its potential as both a biomarker and a therapeutic target. These observations suggest that XPO5 can play dual roles—functioning either as an oncogene or a tumor suppressor—depending on cellular context and tissue type."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "38"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Elsebet Lund, Stephan Güttinger, Angelo Calado, et al. 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